Dostarlimab-gxly

LONDON, UK I December 20, 2024 I GSK plc (LSE/NYSE: GSK) today announced headline results from the FIRST-ENGOT-OV44 phase III trial evaluating Zejula (niraparib) and Jemperli (dostarlimab) in first line advanced ovarian cancer. The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said : “As part of our focus in gynaecological cancers, we continue to evaluate the potential of this combination and look forward to sharing full results from the trial.” The key secondary endpoint of overall survival (OS) did not meet statistical significance. Further analyses are ongoing and data will be shared with health authorities and presented at an upcoming scientific meeting. The safety and tolerability profile was generally consistent with the known safety profiles of the individual agents. About ovarian cancer Ovarian cancer is the eighth most common cancer in women worldwide. 1 Despite high response rates to platinum-based chemotherapy in the first-line setting, approximately 85% of patients will experience disease recurrence. Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence. 2 About the FIRST trial The FIRST-ENGOT-OV44 trial is an international, double-blind, randomised phase III ENGOT trial sponsored by GSK and led by GINECO, a French cooperative group dedicated to gynecological oncology. FIRST is investigating the addition of dostarlimab to both, standard of care (SOC) platinum-based chemotherapy and niraparib maintenance, with or without bevacizumab, as a first-line treatment of stage III or IV nonmucinous epithelial ovarian cancer. Originally, participants were randomised 1:1:2 into three groups: Arm 1: SOC chemotherapy followed by placebo maintenance; Arm 2: SOC chemotherapy followed by niraparib maintenance; Arm 3: SOC chemotherapy and dostarlimab followed by niraparib and dostarlimab maintenance. Bevacizumab could be added at the investigator’s discretion across all arms. Due to the approvals of PARP inhibitors in the first-line setting, Arm 1 (n=193) was closed and participants were subsequently randomized 1:2 to Arms 2 (n= 385) and 3 (n= 753) only. The primary endpoint is investigator-assessed PFS in Arms 2 and 3. Secondary endpoints include OS, PFS2, time to first and second subsequent therapy. ABOUT GINECO 3 GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCa (Institut National du Cancer or French NCI) developing and conducting gynecological and metastatic breast cancer clinical trials at the national and international level. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). About ENGOT 4 The European Network for Gynaecological Oncological Trial (ENGOT) groups is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Currently, ENGOT consists of 21 trial groups from 31 European countries that perform cooperative clinical trials. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial. About Jemperli (dostarlimab) Jemperli , a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development prgramme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies for gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes. In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli , and cobolimab (GSK4069889), a TIM-3 antagonist. Important Information for Jemperli in the EU Indications Jemperli is indicated: Refer to the Jemperli EMA Reference information for a full list of adverse events and the complete important safety information in the EU. About Zejula (niraparib) Zejula is an oral, once-daily Poly (ADP-ribose) polymerase (PARP) inhibitor indicated in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy and who have been selected based on a US FDA-approved companion diagnostic for Zejula . Important Information for Zejula in the EU Indications Zejula is indicated: Refer to the Zejula EMA Reference Information for a full list of adverse events and the complete important safety information in the EU. GSK in oncology Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline

庆祝肿瘤瞭望原创文章突破10000篇 肿瘤瞭望 2024年12月20日 研究 乳腺癌诊疗新动态 领域新观念，星海曼月刊 星海曼月刊·SABCS特辑 刊号：NO.002 领域新观念，星海曼月刊。为了分享乳腺癌诊疗领域最新研究动态，大连医科大学附属第二医院李曼教授携手“肿瘤瞭望”开辟“星海曼月刊”专栏，每月为读者带来深入浅出的文献解析。 时值第47届圣安东尼奥乳腺癌研讨会(SABCS)圆满落幕之际，全球乳腺癌诊疗迎来诸多前沿进展。“星海曼月刊”特别推出SABCS特辑，李曼教授与张蓝心医生共同聚焦BRCA基因胚系突变(gBRCAm)对乳腺癌预后影响，分享OlympiA研究最新数据进展，展望TBCRC 056研究为PARP抑制剂(PARPi)带来了更多可能。 01 GS1-08. BRCA BCY协作组研究：携带gBRCAm的年轻乳腺癌患者行降低风险手术能否改善生存？ 点评 李曼教授：gBRCAm是导致年轻乳腺癌发生、发展的重要遗传因素。降低风险手术包括RRM及RRSO，已被证明可降低乳腺癌进展的风险，但对于生存结局是否获益仍未可知。这项大型国际、多中心研究的结果向我们展示了对于携带gBRCAm的年轻乳腺癌患者，这两种手术均有效降低了OS、DFS及BCFI的风险，显著改善了此类患者的生存预后。但值得注意的是，RRSO在携带gBRCA1m的乳腺癌患者中进行可能获益更多，而对于携带gBRCA2m患者获益的循证医学证据目前尚不充分。 02 GS1-09. OlympiA研究-更新长期随访结果 点评 李曼教授：BRCA基因编码产物参与DNA损伤同源重组修复，gBRCA1/2m会引起同源重组缺陷(HRD)，可与PARPi产生合成致死效应，即当BRCA1/2m引起HRD时，PARP能代偿BRCA的修复作用，而当两种DNA损伤修复途径均出现障碍，则促进肿瘤细胞凋亡。OlympiA研究是奠定了PARPi治疗gBRCAm突变乳腺癌的主要研究之一，在乳腺癌治疗史上具有重要地位。该研究经过中位6.1年的长期随访，证实了对于HER2阴性、携带gBRCAm且具有高复发风险的早期乳腺癌患者，在完成（新）辅助治疗后使用1年奥拉帕利强化治疗能够带来持续的显著获益，并且安全可控，毒性可耐受。 03 RF3-01. TBCRC 056研究：PARPi联合抗PD-1单抗新辅助治疗BRCA突变或PALB2突变ER+/HRE2-乳腺癌队列的结果 点评 李曼教授：PARPi已获得批准用于治疗携带gBRCA1/2m的晚期和早期治疗乳腺癌患者，并且在携带gPALB2m的患者中也初步显示出了疗效。临床前数据表明，PARPi的暴露可导致肿瘤内促炎性cGAS/STING通路的激活，通过招募更多CD8+ T细胞使得携带gBRCAm的肿瘤对免疫治疗敏感。基于此，TBCRC 056对PARPi与抗PD-1联合治疗进行了尝试，在HR+队列中取得了18.8%的pCR率，并且在第3周观察到sTILs平均绝对值增加了11.9%，为携带gBRCAm的HR+早期乳腺癌新辅助治疗提供一种新型联合治疗候选方案，未来期待后续研究数据进一步更新，不断优化HR+乳腺癌新辅助治疗新格局。 圣安东尼奥年会进展频频，在胚系BRCA基因突变领域为我们带来了更多突破，既巩固了当前PARP抑制剂的地位，还开拓了未来乳腺癌领域的科研思路，期待未来更多的研究能够开花结果，进一步推动乳腺癌诊疗水平提升。 专家简历 李曼 教授 医学博士，教授，博士研究生导师 大连医科大学附属二院肿瘤学科主任、教研室主任 I期临床试验病房主任 辽宁省特聘教授、辽宁省百千万人才百人层次中国临床肿瘤学会常务理事 中国抗癌协会乳腺肿瘤整合康复专业委员会副主任委员 中国临床肿瘤学会乳腺癌专家委员会常务委员 中国抗癌协会乳腺癌专业委员会常务委员 辽宁省医学会肿瘤分会副主任委员 辽宁省抗癌协会乳腺癌专业委员会副主任委员 大连市医学会肿瘤分会主任委员 张蓝心 医生 大连医科大学附属第二医院 住院医师、临床医学博士 获得“石力绽放，乳此美好”中青年医师病例演讲大赛辽宁省冠军 研究方向：乳腺癌耐药、转移 2021年参加ESMO大会壁报交流展示，研究成果同步收录于Annals of Oncology杂志 于2022年、2023年ASCO大会发表研究论文2篇，并同步收录于Journal of Clinical Oncology杂志 第一作者发表SCI论文3篇，累计影响因子18.6分 ▌参考文献： [1]. Matteo Lambertini, Amir Sonnenblick, Elisa Agostinetto, et al. Association Between Risk-Reducing Surgeries and Survival in Young BRCA Carriers with Breast Cancer: Results from an International Cohort Study. 2024 SABCS GS1-08. [2]. Judy Garber, et al. OlympiA: A phase 3, Multicenter, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib after (Neo)Adjuvant Chemotherapy in Patients w/ Germline BRCA1 & BRCA2 Pathogenic Variants & High-Risk HER2-Negative Primary Breast Cancer: Longer Term Follow. 2024 SABCS GS1-09. [3]. Erica Mayer, et al. TBCRC 056: A Phase II Study of Neoadjuvant Niraparib with Dostarlimab for Patients with BRCA- or PALB2-Mutated Breast Cancer: Results From the ER+/HER2- Cohort. 2024 SABCS RF3-01. 精彩推荐 1 星海曼月刊丨李曼教授团队：静观HR+晚期乳腺癌PI3Ki、AKTi发展，前瞻PAM通路抑制剂耐药机制 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。